We are interested in the mechanism of lymphoproliferation of T-cells and the main thrust of our work is to use HTLV-I in vitro to understand the viral and cellular factors involved in T-cell transformation. In the case of HTLV-I, we have focused on a viral protein (p12I) of 12 kD, which is a small oncogene and binds to the IL-2R and c chains. We have found that this interaction results in a very small effect on STAT5 activation and hypothesized that this effect may be important in vivo. In addition, we have demonstrated that p12I exists in two alleles in nature (found in patient samples): one carries in position 88 a Lysine and is ubiquitinated and has a half-life of a half of an hour whereas the other natural allele carries an Arginine in position 88 and is very stable. An additional new finding is that p12I binds to the free MHC I heavy chain and interferes with its association with the 2 microglobulin. The working hypothesis is that this viral protein, proven necessary for in vivo infectivity in animal models, may interfere with class I antigen presentation and therefore favors the establishment of the lifelong chronic infection, typical of HTLV-I. During this year, we also discovered a new virus in a pig-tailed macaque with Sezary syndrome. This virus, like the human EBV, phylogenetically belongs to the lymphocryptoviruses. This virus (HVMNE) was isolated from lymphomatous CD8+ T-cell lines, generated from the blood and skin of this diseased animal. Upon inoculation in rodents, HVMNE causes lymphomatous with high frequency, thus providing a small- animal model for lymphoma whereby to assess therapeutic approaches. - HTLV-I, animal models, T-cell transformation, EBV-like virus,